6770-41-8Relevant articles and documents
Multivalent Thiosialosides and Their Synergistic Interaction with Pathogenic Sialidases
Brissonnet, Yoan,Assailly, Coralie,Saumonneau, Amélie,Bouckaert, Julie,Maillasson, Mike,Petitot, Clémence,Roubinet, Benoit,Didak, Blanka,Landemarre, Ludovic,Bridot, Clarisse,Blossey, Ralf,Deniaud, David,Yan, Xibo,Bernard, Julien,Tellier, Charles,Grandjean, Cyrille,Daligault, Franck,Gouin, Sébastien G.
, p. 2358 - 2365 (2019)
Sialidases (SAs) hydrolyze sialyl residues from glycoconjugates of the eukaryotic cell surface and are virulence factors expressed by pathogenic bacteria, viruses, and parasites. The catalytic domains of SAs are often flanked with carbohydrate-binding module(s) previously shown to bind sialosides and to enhance enzymatic catalytic efficiency. Herein, non-hydrolyzable multivalent thiosialosides were designed as probes and inhibitors of V. cholerae, T. cruzi, and S. pneumoniae (NanA) sialidases. NanA was truncated from the catalytic and lectinic domains (NanA-L and NanA-C) to probe their respective roles upon interacting with sialylated surfaces and the synthetically designed di- and polymeric thiosialosides. The NanA-L domain was shown to fully drive NanA binding, improving affinity for the thiosialylated surface and compounds by more than two orders of magnitude. Importantly, each thiosialoside grafted onto the polymer was also shown to reduce NanA and NanA-C catalytic activity with efficiency that was 3000-fold higher than that of the monovalent thiosialoside reference. These results extend the concept of multivalency for designing potent bacterial and parasitic sialidase inhibitors.
Neuramindase Inhibitor
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Page/Page column 11, (2008/12/05)
There are provided a novel compound having irreversible inhibitory activity against neuraminidase, a therapeutic agent and a detection agent for a disease involving neuraminidase. A compound represented by the following formula (I) and a salt thereof, a production method thereof, and an application method thereof, wherein: A1 represents an aryl group optionally having a substituent group or a heteroaryl group optionally having a substituent group;A2 represents —CX2R6 or —CHXR6 wherein X represents —F, —Cl, —Br, or —I;R1 represents a hydrogen atom or an alkyl group optionally having a substituent group;R2, R3, R4, and R5 represent each independently —OC(═O)R6, —OR6, —N(R6)2, —N3, —NHC(═NH)NHR6, —NHCOR6, —OSO3R6, —OPO3(R6)2, F, Cl, Br, or I; andR6 represents each independently a hydrogen atom, an alkyl group optionally having a substituent group, an aryl group optionally having a substituent group, or an optionally substituted heteroaryl group.
Structural Transformations of N-Acetylneuraminic Acid, XXV: Synthesis of Methyl-2-α-glycosides of 4-Epi-, 7-Epi-, 8-Epi-, and 7,8-Bis-epi-N-acetylneuraminic Acid
Bandgar, B. P.,Zbiral, E.
, p. 1075 - 1088 (2007/10/02)
The α-methylketoside of N-acetylneuraminic acid methylester (4) is transformed via the deacetylated compound 5 into the 9,8-O-isopropylidenderivative 6 which could be oxidized regioselectively by RuO4 to the corresponding 4-oxo-sialic acid analogue 7.Reduction with the borane-ammonia complex produces a 1:1 mixture of 6 and the desired α-methylketoside of 9,8-O-isopropyliden-4-epi-N-acetyl-neuraminic acid methylester (8).Removing of the isopropylidene group gives the α-methylketoside of 4-epi-N-acetylneuraminic acid methylester (9), which was further transformed to the ammonium salt of 4-epi-N-acetylneuraminic acid α-methylketoside (10).On the other hand compound 5 was turned into the 4,8,9-tri-O-t-butyldimethylsilylderivative 11a from which the corresponding 7-oxo-compound 12 by oxidation with RuO4 derives.The reduction of 12 with BH3-NH3 yielded a 1:1 mixtures of the starting material 11a and the desired 7-epi-derivative 13a which gives either via the purified peracetylated α-methylketoside of 7-epi-N-acetylneuraminic acid methylester (14) or a direct saponification the sodium salt of 7-epi-N-acetylneuraminic acid-α-methylketoside (15).Applying the Koenigs-Knorr procedure to the peracetylated 8-epi-N-acetylneuraminic acid methylester (16) gives rise to the formation of a 1:1 mixture of the corresponding α- and β-methylketosides 17 and 18 besides traces of the corresponding 2,3-dideoxy-2,3-didehydro-sialic acid derivative 19.After chromatographic separation of 17 further saponification leads to the sodium salt of 8-epi-N-acetylneuraminic acid-α-methylketoside (20).In an analogous procedure the sodium salt of 7,8-di-epi-N-acetylneuraminic acid-α-methylketoside (25) was prepared starting from the peracetylated 7,8-di-epi-N-acetylneuraminic acid methylester (21), whereby a mixture of the α- and β-methylketosides 22 and 23 was formed in a ratio 95:5 besides traces of the peracetylated 2,3-dideoxy-2,3-didehydro-sialic acid methylester (24).Keywords.Sialic acid analogoues; Methyl-α-ketosides of sialic aicd analogues.
